Biology Reference
In-Depth Information
moblasts; cell division ceases with development of the orthochromatic nor-
moblast. In the next step, the nucleus is extruded and because of the presence
of residual strands of RNA (reticulin), the anuclear cell is referred to as a retic-
ulocyte. Over the next 24-48 hours, a further decrease in size and loss of some
reticulin precedes the exit of the cell from the bone marrow. These reticulo-
cytes may be retained in the spleen for 36-48 hours where adhesion molecules
and residual reticulin are removed. The time from pronormoblast to mature
erythrocyte is approximately seven days. When there is an acute demand for
increased red cell production, this interval may be shortened by reducing the
intermitotic interval or by skipping a mitotic division.
Failure of red cell production may occur as one component of a generalized
bone marrow aplasia due to stem cell failure or appear as an isolated defect, a
“pure red-cell aplasia” [12]. Congenital red cell aplasia (Diamond-Blackfan
Syndrome) probably encompasses a number of gene mutations reflected as
molecular defects in cells at the level of CFU-GEMM, BFU-E, and CFU-E
[13]. Acquired red cell aplasia most commonly results from immunologic
blockade of erythropoiesis at the level of BFU-E and CFU-E by T cells or
antibody. IgG antibodies capable of inhibiting BFU-E or CFU-E colony for-
mation can be demonstrated in about half of these patients [12].
Immunologically induced aplasia may occur in association with thymomas,
lymphomas, and some non-hematologic tumors. A pure red cell aplasia asso-
ciated with the development of anti-EPO antibodies inhibitory to erythroid
colony formation has been documented in patients with renal disease receiv-
ing recombinant human erythropoietin (rHuEPO) [14]. (See Chapter 14 for
further information.)
Parvovirus B19, a single-stranded DNA virus, is the etiological agent of the
childhood exanthem fifth disease. The blood group P antigen on the red cell
membrane is the receptor for the virus. B19 replicates only in P antigen-posi-
tive erythroid progenitor cells and is directly cytotoxic in these cells [15].
Suppression of erythropoiesis by B19 infection usually persists for only one to
two weeks, until the viremia is cleared by the immune response. In the pres-
ence of a normal red cell life-span, this transient red cell aplasia is of little clin-
ical importance. In patients with a compensated hemolytic process and a short
red cell life-span, however, the decrease in hemoglobin concentration can be
precipitous, resulting in an “aplastic crisis”.
EPO synthesis
EPO, a 35 Kd glycoprotein, is the primary humoral regulator of erythropoiesis,
promoting both proliferation and survival of erythroid precursors. EPO pro-
duction is regulated by tissue oxygenation. Approximately 90% of EPO is syn-
thesized in renal peritubular interstitial cells that respond to an oxygen-sensing
mechanism, an hypoxia-response pathway that is upregulated by oxygen dep-
rivation. In response to hypoxia, additional EPO-producing peritubular cells
